Recent selective staining techniques produce chromosome specific banding patterns which presumably reflect molecular differentiation of the chromosomes. This proposal outlines a series of experiments employing selective staining techniques to study the molecular organization of human chromosomes. Our preliminary tests with the synthetic polynanion, polystyrene sulfonate, have shown an alteration in the quinacrine banding pattern, but not in the Giemsa banding pattern, of human chromosomes. Prefixation treatments with this polyanion removes specific histone fractions sequentially, and permit tests of the importance of each of these fractions in the production of banding with modified Giemsa methods or with fluorochromes (especially quinacrine, quinacrine mustard and ethidium bromide). The demonstration of qualitative and quantitative differentiation in histone content would be important theoretically in regard to both chromosome structure and genetic regulatory mechanisms, and of practical significance in improving the resolution in the banding pattern. The often-noted similarities between chromosome banding and chromosome spiralization will be analyzed by loosening or tightening the coiling of the chromosome with special pretreatments. An attempt will also be made to distinguish between types of heterochromatin in man by correlating specific staining responses with differential labelling with H3-thymidine and H3-deoxycytidine, and differential reactivity, as described by Shiraishi, of human chromosomes to cold treatment. An extension of differential staining of human pachytene chromosomes is expected to aid materially in chromosome identification and thus permit a much more precise analysis, chromomere by chromomere, of deficiencies, translocations and inversions.